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利用 RNA 干扰技术阻断 ADAM10 的表达抑制腺样囊性癌细胞的生长和转移。

Inhibiting adenoid cystic carcinoma cells growth and metastasis by blocking the expression of ADAM 10 using RNA interference.

机构信息

Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China.

出版信息

J Transl Med. 2010 Dec 20;8:136. doi: 10.1186/1479-5876-8-136.

Abstract

BACKGROUND

Adenoid cystic carcinoma is one of the most common types of salivary gland cancers. The poor long-term prognosis for patients with adenoid cystic carcinoma is mainly due to local recurrence and distant metastasis. Disintegrin and metalloprotease 10 (ADAM 10) is a transmembrane protein associated with metastasis in a number of diverse of cancers. The aim of this study was to analyze the relationship between ADAM 10 and the invasive and metastatic potentials as well as the proliferation capability of adenoid cystic carcinoma cells in vitro and in vivo.

METHODS

Immunohistochemistry and Western blot analysis were applied to detect ADAM 10 expression levels in metastatic cancer tissues, corresponding primary adenoid cystic carcinoma tissues, adenoid cystic carcinoma cell lines with high metastatic potential, and adenoid cystic carcinoma cell lines with low metastatic potential. RNA interference was used to knockdown ADAM 10 expression in adenoid cystic carcinoma cell lines with high metastatic potential. Furthermore, the invasive and metastatic potentials as well as the proliferation capability of the treated cells were observed in vitro and in vivo.

RESULTS

It was observed that ADAM 10 was expressed at a significantly higher level in metastatic cancer tissues and in adenoid cystic carcinoma cell lines with high metastatic potential than in corresponding primary adenoid cystic carcinomas and adenoid cystic carcinoma cell lines with low metastatic potential. Additionally, silencing of ADAM 10 resulted in inhibition of cell growth and invasion in vitro as well as inhibition of cancer metastasis in an experimental murine model of lung metastases in vivo.

CONCLUSIONS

These studies suggested that ADAM 10 plays an important role in regulating proliferation and metastasis of adenoid cystic carcinoma cells. ADAM 10 is potentially an important therapeutic target for the prevention of tumor metastases in adenoid cystic carcinoma.

摘要

背景

腺样囊性癌是最常见的唾液腺癌之一。腺样囊性癌患者的长期预后较差,主要是由于局部复发和远处转移。解整合素金属蛋白酶 10(ADAM10)是一种与多种癌症转移相关的跨膜蛋白。本研究旨在分析 ADAM10 与体外和体内腺样囊性癌细胞的侵袭和转移潜能以及增殖能力之间的关系。

方法

应用免疫组织化学和 Western blot 分析检测转移性癌组织、相应的原发性腺样囊性癌组织、高转移潜能的腺样囊性癌细胞系和低转移潜能的腺样囊性癌细胞系中 ADAM10 的表达水平。采用 RNA 干扰技术敲低高转移潜能的腺样囊性癌细胞系中 ADAM10 的表达。此外,观察处理细胞的体外侵袭和转移潜能以及体内增殖能力。

结果

观察到 ADAM10 在转移性癌组织和高转移潜能的腺样囊性癌细胞系中的表达水平明显高于相应的原发性腺样囊性癌组织和低转移潜能的腺样囊性癌细胞系。此外,沉默 ADAM10 可抑制体外细胞生长和侵袭,并抑制体内实验性肺转移小鼠模型中的癌症转移。

结论

这些研究表明,ADAM10 在调节腺样囊性癌细胞的增殖和转移中起重要作用。ADAM10 可能是预防腺样囊性癌肿瘤转移的重要治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b246/3017514/4ccaeb7e45a9/1479-5876-8-136-1.jpg

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